Previous work (CF. Summary and Review Section, hereafter attached) in this laboratory indicated that the connective tissue disorder present in chondrodysplastic Alskan Malamutes is secondary to other more fundamental changes in metabolism. Preliminary studies furnished evidence that there was decreased absorption of zinc and copper from the gut as well as increased levels of tissue storage of copper and iron. All our data suggest that increased tissue levels were due to decreased mobilization of these metals. This could account for the change in connective tissue metabolism and the anaemia observed. The proposed research seeks to characterize and establish the metabolic disorder in the metabolism of zinc, copper and/or iron in order to establish the site of the genetic lesion. The objectives of the project are: 1) To characterize the dynamics of copper, zinc and iron metabolism in normal and chondrodysplastic Alaskan Malamutes. 2) To characterize the molecules which bind these ions in the storage tissues in which higher than normal levels of these metals have been found. The characterization will include such things as molecular weights, ion capacity and binding rates. The methods for achieving these objectives are deteiled later; however, they can be summarized as follows. The dynamics of the trace minerals will be followed by use of the appropriate radioactive tracers. The transport and storage forms will be separated using gel chromatography and the appropriate radioactive tracer. The fractions which contain the metal of study will be characterized by their molecular weights, isoelectric points and mineral content. The binding capacity and affinities of these fractions for zinc, copper and iron will also be studied.